PROJECT SUMMARY/ABSTRACT This project responds to the need identified by NIDCR to develop improved methods to detect and predict progression of dental caries (tooth decay) to improve human health. Worldwide, caries is the most common chronic disease affecting almost everyone. Dental disease is a major cause of economic and social loss and leads to complications including pain, tooth loss and even death. Generally inactive lesions require no treatment while active lesions do. Early active lesions permit conservative treatment, whereas cavitated lesions require more costly and invasive restoration. Since the early 40?s, caries diagnosis has been performed visually and using a dental explorer, but early cavities are missed and the explorer can cause cavitation. Alternatively, X- Rays identify more fully developed cavities but are unable to identify early forming lesions. Newer methods for caries diagnosis show little benefit and incur greater cost to dentist and patient. Current methods diagnose a surface defect in the enamel but cannot distinguish ?activity?, a critical need in modern dentistry. Our goal is to develop a new clinically valid test to diagnose early and active carious lesions that also enables effective monitoring of conservative treatment. We have invented a nanoparticle technology which specifically targets active carious lesions. The nanoparticles are made from food grade corn starch and have been functionalized to specifically target the subsurface of carious lesions. They are tagged with a safe fluorescent dye so the caries will illuminate and be easily seen using a standard dental curing lamp, allowing dentists to quickly differentiate whether a carious lesion is active or inactive and to monitor treatment results. The product is a mouth rinse or oral gel containing a low concentration of the nanoparticles in water, enabling visual detection of early active carious lesions otherwise invisible on the tooth surface, because the extremely small nanoparticles can penetrate through surface microchannels into the early active sub-surface lesion. The starch-based nature of the nanoparticles facilitates rapid degradation by amylase enzyme present in human saliva, so teeth will no longer fluoresce upon leaving the dentist?s office. With earlier detection of caries and treatment of the disease before cavitation occurs, invasive treatments will be prevented, resulting in the enablement of Minimally Invasive Dentistry and improved oral health. Our Phase I research has demonstrated the potential of this technology, and the functionalities on the nanoparticles were successfully optimized to provide a viable product with sufficient targeting and fluorescence contrast to be macroscopically visible by the dental professional on various tooth surfaces when using a standard dental curing light available in a dental practice. Phase II involves in vitro assessment of the test?s diagnostic capabilities including in vitro sensitivity and specificity, in vivo biocompatibility and studies required for FDA submission, clinical feasibility, and scaling of production. Successful completion of the Phase II Aims will facilitate commercialization in Phase III, and meet clinical development, regulatory and manufacturing milestones to support clinical validation and longitudinal clinical outcome studies.